■吸烟是吸烟者严重疾病的原因,包括心血管疾病.通过内皮功能障碍的途径,脂质浸润,巨噬细胞募集和血管重塑,动脉粥样硬化是大多数心血管疾病发展的基础。越来越多的下一代产品(NGP)为成年吸烟者提供潜在的减少伤害的尼古丁递送形式。本研究旨在优化体外心血管模型以评估此类产品。在流动条件下将人冠状动脉内皮细胞(HCAEC)与THP-1单核细胞组合在OrganoPlate®2-泳道芯片(MimetasBV)上培养。
■将来自1R6F参考香烟的水性气溶胶提取物与两类NGP进行了比较,(加热烟草产品(HTP)和电子尼古丁输送系统(ENDS)),评估对选定动脉粥样硬化终点的相对影响(氧化应激,单核细胞粘附,ICAM-1表达,和炎症标记物)。THP-1单核细胞与水提取物接触后,然后将得到的条件培养基加入到HCAEC容器中。
■1R6F始终是最有效的测试文章,在比应用于HTP和ENDS两者的浓度低4倍的浓度下引发观察到的响应。在所有端点中,HTP比ENDS产品更有效,然而,所有供试品增加单核细胞粘附。ICAM-1似乎不是单核细胞粘附的主要驱动因素,然而,这可能是由于复制变异性。与仅提取对照曝光相比,THP-1-培养基预处理是观察到的反应的重要介质。
■总而言之,数据表明NGP提取物,与香烟相比,在与动脉粥样硬化相关的早期关键事件中,含有主要气溶胶化学成分的生物活性显着降低,增加了此类产品减少烟草危害潜力的证据。
UNASSIGNED: Smoking cigarettes is a cause of serious diseases in smokers, including cardiovascular disease. Through a pathway of endothelial dysfunction, lipid infiltration, macrophage recruitment and vascular remodeling, atherosclerosis is fundamental in the development of most cardiovascular diseases. There is an increasing number of next-generation products (NGP) which provide potentially reduced harm forms of nicotine delivery to adult smokers. This study aimed to optimise an in vitro cardiovascular model to assess such products. Human Coronary Artery Endothelial Cells (HCAECs) were cultured on an OrganoPlate®2-lane chip (Mimetas BV) combined with THP-1 monocytes under flow conditions.
UNASSIGNED: An aqueous aerosol extract from the 1R6F reference cigarette was compared with two categories of NGP, (a heated tobacco product (HTP) and an electronic nicotine delivery system (ENDS)), to assess relative effects on select atherogenic endpoints (oxidative stress, monocyte adhesion, ICAM-1 expression, and inflammatory markers). Following exposure of THP-1 monocytes with the aqueous extracts, the resulting conditioned medium was then added to the HCAEC vessels.
UNASSIGNED: 1R6F was consistently the most potent test article, eliciting observed responses at 4x lower concentrations than applied for both the HTP and ENDS. The HTP was more potent than the ENDS product across all endpoints, however, all test articles increased monocyte adhesion. ICAM-1 did not appear to be a main driver for monocyte adhesion, however, this could be due to replicate variability. Upon comparison to an extract-only control exposure, THP-1-medium pre-conditioning was an important mediator of the responses observed.
UNASSIGNED: In conclusion, the data suggests that the NGP extracts, containing primary aerosol chemical constituents exhibit a marked reduction in biological activity in the early key events associated with atherogenesis when compared to a cigarette, adding to the weight of evidence for the tobacco harm reduction potential of such products.